Breath actuated aerosol dispensers

ABSTRACT

A breath actuated metered dose inhaler device for use wit an aerosol valve having a transient metering chamber.

This invention relates to breath actuated medicament dispensing devicesof the type where a metered dose of medicament is administered to therespiratory system of a patient in response to the inhalation of thepatient.

Metering valves are a common means by which aerosols are dispensed fromaerosol containers. Metering valves are particularly useful foradministering medicinal formulations that include a liquefied gaspropellant and are delivered to a patient in an aerosol.

In some metering valves, the metering chamber fills with the medicinalformulation prior to the patient actuating the valve stem and therebyreleasing the dose. The metering chamber is refilled with formulationafter dispensing one dose so that the metering valve is ready todischarge the next dose. Consequently, the metering chamber containsformulation at all times except for the brief time during which thevalve stem is depressed by the user to discharge a dose.

In other metering valves the metering valve is designed such that themetering chamber does not materialise unless and until the valve stem isactuated. Examples of such valves are disclosed in U.S. Pat. No.4,819,834. Actuation of these valve stems can be divided into a fillingstage and a discharge stage. The filling stage begins as the valve stemis depressed during actuation. The action of depressing the valve stemcauses the formation of a transient metering chamber, which is in fluidcommunication with the residual metering volume defined by the smallannular gap. As the valve stem is depressed, the transient portion ofthe metering chamber expands and formulation enters the meteringchamber. As displacement of the valve stem continues, a stage is reachedat which filling of the transient metering chamber stops.

Eventually, displacement of the valve stem continues to the dischargestage, in which the metered formulation is discharged. In these valves,a single actuation thus causes rapid filling of the transient meteringchamber followed by discharge of the formulation to the patient.Generally, metered formulation does not reside for any appreciableamount of time in the metering chamber in these metering valves.

While a metering valve having a transient metering chamber providesadvantages over other types of metering valves for the delivery ofaerosol formulations, it has now been appreciated that the flow offormulation from the container to the metering chamber may be disruptedor impeded. Flow through regions of significantly restricted access,such as narrow annular passageways and/or entrance ways to the meteringchamber, may be impeded sufficiently to give rise to substantiallyincomplete filling of the metering chamber. If this happens, formulationmay be delivered in inconsistent or inaccurate doses. In particular, ithas now been appreciated that the time available for filling themetering chamber also has a significant effect on the ability tocompletely fill the transient metering chamber. The time available forfilling depends on the speed at which the valve stem is depressed. Inthe so-called “press-and-breathe” devices in which the patient manuallydepresses the aerosol container relative to the valve stem to fire thevalve the speed at which the valve stem is depressed is generally notmore than 100 mm/sec. However, breath actuated inhalers typically firethe valve more rapidly than manual firing e.g. with valve stem speeds inthe range 165 to 330 mm/sec. Thus, there are difficulties associatedwith the use of metering valves having a transient metering chamber withbreath actuated devices.

A common feature of many known breath actuation devices is that theyinvolve two stages of operation: a priming stage in which a primingforce is applied to the valve stem but actuation of the valve stem isprevented; and a firing stage in which the priming force is releasedresulting in movement of the valve stem to fire the valve. The primingstage is generally a manual operation and may involve some movement ofthe valve stem but not sufficient to fire the valve. Any movement of thevalve stem in the priming stage tends to be at relatively low speed.Once the device is triggered by inhalation there is high speeddisplacement of the valve stem under the priming force.

It has now been found that if the metering and firing stages ofoperation of a metering valve of the type having a transient meteringchamber are synchronised with the priming and firing stages of a breathactuated device, any difficulties or problems associated with flow offormulation to fill the metering chamber may be overcome or at leastsignificantly reduced.

Therefore according to the present invention there is provided a breathactuated medicament dispensing device comprising:

an aerosol container containing a pressurised medicament formulationequipped with a metered dose dispensing valve having a movable valvestem;

a housing disposed about the aerosol container;

a patient port in communication with the dispensing valve;

priming means adapted to apply a bias to the valve stem relative to theaerosol container sufficient to move the valve stem to fire the valve;restraining means movable between a blocking position in which itprevents said bias firing the valve and a release position in which itallows said bias to fire the valve;

trigger means responsive to inhalation through the patient port to causethe restraining means to move from its blocking position to its releaseposition; wherein the aerosol valve comprises:

a valve housing;

a tank component positioned within the valve housing; and

a valve stem mounted within said valve housing and tank componentsequentially movable between a first position, a second position and athird position as the valve stem is depressed in a single direction;

such that:

as the valve stem is moved from said first position towards, said secondposition a metering chamber is formed and defined between the valve stemand tank component and formulation flows from the aerosol container intothe metering chamber;

in said second position the metering chamber has a predetermined volumeand is sealed from the aerosol container; and

in said third position formulation is released from the metering chamberthrough the valve stem; and wherein:

the priming means is constructed and arranged such that as the device isprimed by operating said priming means the valve stem is moved from itsfirst to its second position to allow formation and filling of themetering chamber;

the restraining means is constructed and arranged such that in itsblocking position it maintains the valve stem in its second positionuntil the trigger means is actuated by inhalation through the patientport.

The invention provides a simple effective means of overcoming problemsassociated with filling the metering chamber of an aerosol valve of thetype having a transient metering chamber by controlling the movement ofthe valve stem from its first to second position by the priming andrestraining means of a breath actuated device. When the breath actuateddevice has been primed the valve stem is held in its second positionwith the metering chamber completely full of formulation ready to bedispensed. The priming stage of the breath actuated device issufficiently slow to allow the metering chamber to be filled as it iscreated by movement of the valve stem.

The invention is applicable to a wide range of breath actuated devicesincluding those in which the restraining means comprises a latchmechanism and those in which the restraining means comprises means forapplying a resisting pneumatic force.

In general, the aerosol container will be mounted in the dispensingdevice with the valve stem located in a fixed nozzle block. A primingforce is applied to the base of the aerosol container e.g. bycompression of a spring. When the device is primed by compressing thespring e.g. by moving a lever to an over centre position, there ismovement of the aerosol container relative to the valve stem causing thevalve stem to be partially depressed before the restraining means isengaged to prevent further movement. The device is arranged such thatthis initial movement of the valve stem relative to the aerosolcontainer is sufficient to form and completely fill the metering chamberin the valve. The valve is held in its second position until the deviceis actuated by the patient inspiring through the patient port. Patientinspiration actuates the trigger which allows movement of therestraining means to its release position and thereby allows relativemovement of the valve stem and aerosol container under the influence ofthe bias causing the valve to fire.

In another embodiment of the invention the aerosol container is fixedwithin the housing and the priming force is applied to the valve steme.g. to a movable nozzle block which is mounted on the valve stem.

The invention will now be described with reference to the accompanyingdrawings in which:

FIG. 1A represents a vertical cross-section through an embodiment of adispensing device in accordance with the invention in its firstposition,

FIG. 1B shows the restraining and triggering means of the device and

FIG. 1C is a cross-section through the aerosol valve in its firstposition;

FIGS. 2A, 2B and 2C represent similar views to FIG. 1 with the device inits primed position and the aerosol valve in its second position; and

FIG. 3A shows the device of FIG. 1 in its fired position and

FIG. 3B shows the aerosol valve in its third (fired) position.

The invention will be described with reference to a breath actuateddevice which is described in EP 0147028. However, it will be appreciatedthat the invention may use other variants of breath actuated devices,such as those described in GB 1288971, GB 1297993, GB 1335378, GB1383761, GB 1392192, GB 1413285, WO85/01880, GB 2204799, U.S. Pat. No.4,803,978, EP 0186280, GB 1269554, U.S. Pat. No. 5,447,150 and WO01/93933.

In the drawings, like references represent like parts.

FIG. 1A shows a cross section through a breath actuated device in itsrest position. The device comprises an aerosol container (2) containinga pressurised medicament formulation and equipped with a metered dosedispensing valve (4) having a movable valve stem (6). A housing (8) isdisposed about the aerosol container (2) and comprises a sleeve (10),body (12), top (14) and a mouthpiece cover (16) which covers the patientport (18). The valve stem (6) is positioned within a nozzle block (20)which directs formulation from the valve stem towards the patient port(18).

The priming means comprises a priming lever (22) which is pivotallymounted about axis (23) to act upon priming spring (24) secured within acage (26). In the rest position shown in FIG. 1A, the priming spring(24) exerts little or no bias on the aerosol container (2).

The restraining means comprises a rocker (28) pivotally mounted aboutaxis (30). One end of the rocker is attached to tension spring (32) andthe other is pivotally connected to catch (34). The other end of catch(34) rests on a cam surface of vane (36) which acts as the triggermechanism. Vane (36) is pivotally mounted at axis (38).

In the rest position shown in FIG. 1B there is a clearance (40) betweenthe upper surface (42) of the rocker (28) and the lower surface (44) ofthe valve ferrule.

FIG. 1C is on an enlarged scale compared with FIG. 1A and shows across-section through the aerosol valve in its first position when thedevice is in its rest position as shown in FIG. 1A.

The valve (4) comprises a valve housing (46), a tank component (48)positioned within the valve housing and a valve stem (6) mounted withinthe valve housing and tank component. The valve comprises outer seal(50) and inner seal (52). The valve stem (6) is biased towards its firstposition shown in FIG. 1C by compression spring (54) held within springretaining sleeve (56).

The outer portion of the valve stem (6) comprises a discharge passage(58) and side pierce (60). The inner portion of the valve stem is shapedto completely fill the tank component (48) when the valve stem is in itsfirst position. The inner portion of the valve stem is hollow, incommunication with the aerosol container and comprises sampling ports(62). When the valve stem is in its first position shown in FIG. 1Cthere is no metering chamber formed.

FIGS. 2A and 2B show the device in its primed position. Priming lever(22) is pivoted upwardly causing spring (24) to be compressed applying abias to the aerosol container (2). The aerosol container movesdownwardly under the influence of the bias until the lower surface (44)of the valve ferrule contacts the upper surface (42) of the rocker (28).The rocker (28) is unable to pivot since it is blocked by the catch (34)that engages the vane (36). During the priming operation the aerosolcontainer moves by the distance of the clearance (40) shown in FIG. 1B.

During the priming operation the valve moves from its first positionshown in FIG. 1C to its second position shown in FIG. 2C. Duringmovement of the valve stem from its first to its second position ametering chamber (64) is formed between the inner portion of the valvestem (6) and the tank component (48). The metering chamber is filledwith formulation from the aerosol container passing through the samplingport (62) and through a small annular gap (not shown) between the innerportion of the valve stem (6) and the tank component (48) into themetering chamber (64). Formulation is prevented from exiting themetering chamber (64) by the outer seal (50) that is in sealingengagement with the valve stem and between the tank component (48) andthe valve housing (46). In the second position of the valve stem shownin FIG. 2, inner seal (52) is in sealing engagement with the valve stemthereby preventing formulation passing through the sampling port (62).In the second position of the valve stem shown in FIG. 2C the meteringchamber has been fully formed and completely filled with theformulation.

FIG. 3A shows the device in its fired position. Inhalation through thepatient port (18) causes vane (36) to pivot upwardly. Movement of thevane (36) displaces the end of catch (34) from the vane thereby movingthe constraint on rocker (28). Rocker (28) pivots due to the forceexerted on it by the valve ferrule under the influence of the primingspring (24) thereby allowing the aerosol container (2) to movedownwardly, causing the valve to fire.

FIG. 3B shows the valve in its firing position. The valve stem (6) hasmoved inwardly such that the side pierce (60) passes through the outerseal (50) thereby allowing the contents of the metering chamber to passthrough the side pierce (60) and discharge passage (58). The inner seal(52) remains in sealing engagement with the inner portion of the valvestem preventing communication between the metering chamber (64) and theaerosol container.

It will be appreciated that the speed of movement during the firing,i.e. movement of the valve stem from its second to its third position,will not affect the performance of the valve since the metering chamberwas formed and completely filled during the priming stage. Thus highspeed movement under the influence of the priming spring during thefiring operation has no effect on the volume of formulation dispensed.

It will be understood that the present disclosure of particularembodiments in accordance with the invention is for the purpose ofillustration only and the invention extends to modifications, variationsand improvements thereof.

1. A breath actuated medicament dispensing device comprising: an aerosolcontainer containing a pressurised medicament formulation equipped witha metered dose dispensing valve having a movable valve stem; a housingdisposed about the aerosol container; a patient port in communicationwith the dispensing valve; a priming mechanism adapted to apply a biasto the valve stem relative to the aerosol container sufficient to movethe valve stem to fire the valve; a restraining mechanism movablebetween a blocking position in which it prevents said bias firing thevalve and a release position in which it allows said bias to fire thevalve; and a trigger assembly responsive to inhalation through thepatient port to cause the restraining mechanism to move from itsblocking position to its release position; wherein the aerosol valvecomprises: a valve housing; a tank component positioned within the valvehousing; and a valve stem mounted within said valve housing and tankcomponent sequentially movable between a first position, a secondposition and a third position as the valve stem is depressed in a singledirection; such that: as the valve stem is moved from said firstposition towards said second position a metering chamber is formed anddefined between the valve stem and tank component and formulation flowsfrom the aerosol container into the metering chamber; in said secondposition the metering chamber has a predetermined volume and is sealedfrom the aerosol container; and in said third position formulation isreleased from the metering chamber through the valve stem; and wherein:the priming assembly is constructed and arranged such that as the deviceis primed by operating said priming assembly the valve stem is movedfrom its first to its second position to allow formation and filling ofthe metering chamber; the restraining mechanism is constructed andarranged such that in its blocking position it maintains the valve stemin its second position until the trigger assembly is actuated byinhalation through the patient port.
 2. A breath actuated medicamentdispensing device as claimed in claim 1 in which the priming assemblycomprises a spring.
 3. A breath actuated medicament dispensing device asclaimed in claim 1 in which the valve stem is located within a nozzleblock and the priming assembly applies a bias to the aerosol container.4. A breath actuated medicament dispensing device as claimed in claim 1in which the restraining mechanism comprises a latch and the triggeringassembly comprises a vane.
 5. A breath actuated medicament dispensingdevice as claimed in claim 4 in which the vane is positioned within thepatient port.
 6. A breath actuated medicament dispensing device asclaimed in claim 1 in which the restraining mechanism applies aresisting pneumatic force to prevent firing of the valve under theinfluence of the priming assembly.